Anti-IgE Therapy in Asthma and Allergy

76 Pages·2001·1.08 MB·English

by  S.H. Arshad

Anti-IgE Therapy in Asthma and Allergy

Anti-IgE Therapy in
Asthma and Allergy
Syed Hasan Arshad,DM,MRCP
Director of the David Hide Asthma and Allergy Centre,Isle of Wight,
UK and Director of Clinical Trials,Department of Medical
Specialties,Southampton General Hospital,Southampton,UK
K Suresh Babu,MD,DNB
Clinical Research Fellow,Respiratory,Cell and Molecular Biology
Research Division,University of Southampton School of Medicine,
Southampton,UK
Stephen T Holgate,BSc,MD,DSc,FRCP,FRCPath,
FIBiol,CBiol,FmedSci
Medical Research Council Professor of Immunopharmacology at
the University of Southampton,Southampton General Hospital,
Southampton,UK
The views expressed in this publication are
those of the authors and not necessarily
those of Martin Dunitz Ltd.
© 2001 Martin Dunitz Ltd,a member of
the Taylor & Francis group
First published in the United Kingdom in 2001 by
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Cover image:Interactions between CD4 T cells and B cells
that are important in IgE synthesis.Adapted with permission
from Busse WW, Lemanske RF.Advances in immunology:asthma.
NJEM2001;344:353.Copyright © 2001
Massachusetts Medical Society.All rights reserved.
ISBN 0-203-42170-1 Master e-book ISBN
ISBN 0-203-44590-2 (Adobe eReader Format)
Contents
Preface vii
1. What is asthma and allergy? 1
2. What is immunoglobulin E? 10
3. Synthesis and regulation of IgE 18
4. Allergic inflammation and the role of IgE 24
5. Current management of asthma and allergy 31
6. Anti-IgE as a therapeutic strategy 37
7. Efficacy and safety of anti-IgE in asthma 44
8. Efficacy and safety of anti-IgE in allergic rhinitis 51
9. Future prospects for IgE in the treatment of allergic 56
disorders
Further reading 60
Index 63
v

Preface
The discovery by Prausnitz and Küstner in 1921 of reagin,the
circulating substance that could passively transfer the immediate
allergic response from one individual to another,stimulated a
50-year search for the molecular basis of this phenomenon.The
identification of reagin as IgE independently by Ishizakas and
Johansson in the late 1960s provided the rational basis for dis-
eases such as rhinitis,asthma and food allergy and a legitimate
target for novel therapeutics.Almost 25 years were to pass
before it was clearly shown that a monoclonal antibody directed
against that part of the IgE molecule that is encrypted by the
high- and low-affinity IgE receptors on effector cells could dra-
matically remove circulating and tissue IgE by forming small com-
plexes that are easily cleared without cross-linking IgE on the
surface of effector cells and,therefore,failing to produce anaphy-
lactic responses. The fully humanized monoclonal antibody
omalizumab (Xolair™) has these properties.It has been clearly
demonstrated that when administered at 2–4 weekly intervals
this therapy has markedly beneficial effects on multiple outcome
measures in allergic asthma.
This pocketbook provides an illustrative summary of the role of
IgE in asthma and allied allergic disorders and the effects of anti-
IgE treatment.With little new having been introduced into the
armamentarium for asthma therapy in the last three decades
other than improvements in β -adrenoceptor agonists,corticos-
2
teroids and cysteinyl leukotriene antagonists,the introduction of
omalizumab is likely to provide a new way of treating allergic
vii
disorders with effects that extend beyond a single affected organ
and tissue.Its precise role in treatment guidelines will need to be
carefully evaluated, but its clear efficacy and safety provide
a clear statement about the importance of IgE across the full
spectrum of allergic disease.
Syed Hasan Arshad
K Suresh Babu
Stephen T Holgate
March 2001
viii
What is asthma and 1
allergy?
What is asthma?
Asthma is a chronic inflammatory disease of the airways and
manifests clinically as intermittent cough and wheezing in
response to exposure to allergenic and non-allergenic stimuli.
The severity of asthma varies widely among individuals.In most
patients the symptoms are mild and intermittent.However,in
some patients it is a life-threatening disease which severely
affects their quality of life.
The National Heart,Lung,and Blood Institute (NHLBI)/World
Health Organization (WHO) expert panel report defines asthma
as (Figure 1):
a chronic inflammatory disorder of the airways in which many cells
and cellular elements play a role,in particular,mast cells,
eosinophils,T lymphocytes,neutrophils,and epithelial cells.In
susceptible individuals,this inflammation causes recurrent
episodes of wheezing,breathlessness,chest tightness,and cough,
particularly at night and/or in the early morning.These symptoms
are usually associated with widespread but variable airflow
limitation that is at least partly reversible either spontaneously
or with treatment.The inflammation also causes an associated
increase in airway responsiveness to a variety of stimuli.
1